Medicine and Health Sciences Commons^™

Click Display: A Rapid And Efficient In Vitro Protein Display Method For Directed Evolution, Yu Zeng, Michael Woolley, Karuppiah Chockalingam, Benjamin Thomas, Srishtee Arora, Magnus Hook, Zhilei Chen

Faculty, Staff and Student Publications

We describe a novel method for in vitro protein display-click display-that does not depend on maintaining RNA integrity during biopanning and yields covalently linked protein-cDNA complexes from double-stranded input DNA within 2 h. The display is achieved in a one-pot format encompassing transcription, translation and reverse transcription reactions in series. Stable linkage between proteins and the encoding cDNA is mediated by a modified DNA linker-ML-generated via a click chemistry reaction between a puromycin-containing oligo and a cDNA synthesis primer. Biopanning of a click-displayed mock library coupled with next-generation sequencing analysis revealed >600-fold enrichment of target binders within a single round …

All About Me, Emily Kiska Bsn, Rn, Anna Neamand Bsn, Rn, Tianna Popstein Bsn, Rn, Danalyn Roncolato Bsn, Rn, Jade Zamadics Bsn, Rn

Patient Care Services / Nursing

No abstract provided.

Modulation Of The Proteostasis Network Promotes Tumor Resistance To Oncogenic Kras Inhibitors, Xiangdong Lv, Xuan Lu, Jin Cao, Qin Luo, Yao Ding, Fanglue Peng, Apar Pataer, Dong Lu, Dong Han, Eric Malmberg, Doug W Chan, Xiaoran Wang, Sara R Savage, Sufeng Mao, Jingjing Yu, Fei Peng, Liang Yan, Huan Meng, Laure Maneix, Yumin Han, Yiwen Chen, Wantong Yao, Eric C Chang, Andre Catic, Xia Lin, George Miles, Pengxiang Huang, Zheng Sun, Bryan Burt, Huamin Wang, Jin Wang, Qizhi Cathy Yao, Bing Zhang, Jack A Roth, Bert W O'Malley, Matthew J Ellis, Mothaffar F Rimawi, Haoqiang Ying, Xi Chen

Faculty, Staff and Student Publications

Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier to progress. Here, we report proteostasis reprogramming as a key convergence point of multiple KRASi-resistance mechanisms. Inactivation of oncogenic KRAS down-regulated both the heat shock response and the inositol-requiring enzyme 1α (IRE1α) branch of the unfolded protein response, causing severe proteostasis disturbances. However, IRE1α was selectively reactivated in an ER stress-independent manner in acquired KRASi-resistant tumors, restoring proteostasis. Oncogenic KRAS promoted IRE1α protein stability through extracellular signal-regulated kinase (ERK)-dependent phosphorylation of IRE1α, leading to IRE1α disassociation from 3-hydroxy-3-methylglutaryl reductase degradation (HRD1) E3-ligase. In …

A Critical Role For Camkii In Behavioral Timescale Synaptic Plasticity In Hippocampal Ca1 Pyramidal Neurons, Kuo Xiao, Yiding Li, Raymond A Chitwood, Jeffrey C Magee

Faculty, Staff and Students Publications

Behavioral timescale synaptic plasticity (BTSP) is a type of non-Hebbian synaptic plasticity reported to underlie place field formation. Despite this important function, the molecular mechanisms underlying BTSP are poorly understood. The α-calcium-calmodulin-dependent protein kinase II (αCaMKII) is activated by synaptic transmission-mediated calcium influx, and its subsequent phosphorylation is central to synaptic plasticity. Because the activity of αCaMKII is known to outlast the event triggering phosphorylation, we hypothesized that it could mediate the extended timescale of BTSP. To examine the role of αCaMKII in BTSP, we performed whole-cell in vivo and in vitro recordings in CA1 pyramidal neurons from mice engineered …

Sars-Cov-2 Niches In Human Placenta Revealed By Spatial Transcriptomics, Enrico R Barrozo, Maxim D Seferovic, Eumenia C C Castro, Angela M Major, David N Moorshead, Michael D Jochum, Ricardo Ferral Rojas, Cynthia D Shope, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Functional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map of placental transcription could provide direct evidence for niche microenvironments with unique functions and transcription profiles.

METHODS: We utilized Visium Spatial Transcriptomics paired with H&E staining to generate 17,927 spatial transcriptomes. By integrating these spatial transcriptomes with 273,944 placental single-cell and single-nuclei transcriptomes, we generated an atlas composed of at least 22 subpopulations in the maternal decidua, fetal chorionic villi, and chorioamniotic membranes.

FINDINGS: Comparisons of placentae from uninfected healthy controls (n = 4) with COVID-19 asymptomatic …

Mutation Signature Filtering Enables High-Fidelity Rna Structure Probing At All Four Nucleobases With Dms, David Mitchell, Jennifer Cotter, Irfana Saleem, Anthony M Mustoe

Faculty, Staff and Students Publications

Chemical probing experiments have transformed RNA structure analysis, enabling high-throughput measurement of base-pairing in living cells. Dimethyl sulfate (DMS) is one of the most widely used structure probing reagents and has played a pivotal role in enabling next-generation single-molecule probing analyses. However, DMS has traditionally only been able to probe adenine and cytosine nucleobases. We previously showed that, using appropriate conditions, DMS can also be used to interrogate base-pairing of uracil and guanines in vitro at reduced accuracy. However, DMS remained unable to informatively probe guanines in cells. Here, we develop an improved DMS mutational profiling (MaP) strategy that leverages …

Argininosuccinate Lyase Deficiency Causes Blood-Brain Barrier Disruption Via Nitric Oxide-Mediated Dysregulation Of Claudin Expression, Jordan Kho, Urszula Polak, Ming-Ming Jiang, John D Odom, Jill V Hunter, Saima M Ali, Lindsay C Burrage, Sandesh Cs Nagamani, Robia G Pautler, Hannah P Thompson, Akihiko Urayama, Zixue Jin, Brendan Lee

Faculty, Staff and Student Publications

Nitric oxide (NO) is a critical signaling molecule that has been implicated in the pathogenesis of neurocognitive diseases. Both excessive and insufficient NO production have been linked to pathology. Previously, we have shown that argininosuccinate lyase deficiency (ASLD) is a novel model system to investigate cell-autonomous, nitric oxide synthase-dependent NO deficiency. Humans with ASLD are at increased risk for developing hyperammonemia due to a block in ureagenesis. However, natural history studies have shown that individuals with ASLD have multisystem disease including neurocognitive deficits that can be independent of ammonia. Here, using ASLD as a model of NO deficiency, we investigated …

Acculturation And Subjective Norms Impact Non-Prescription Antibiotic Use Among Hispanic Patients In The United States, Lindsey A Laytner, Kiara Olmeda, Juanita Salinas, Osvaldo Alquicira, Susan Nash, Roger Zoorob, Michael K Paasche-Orlow, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Using antibiotics without medical guidance (non-prescription antibiotic use) may contribute to antimicrobial resistance. Hispanic individuals are a growing demographic group in the United States (US) with a high prevalence of non-prescription antibiotic use. We investigated the effects of acculturation and subjective norms on Hispanic individuals’ intentions to use antibiotics without a prescription from the following sources: (1) markets in the United States (not legal), (2) other countries (abroad), (3) leftovers from previous prescriptions, and (4) friends/relatives. We surveyed self-identified Hispanic outpatients in eight clinics from January 2020 to June 2021 using the previously validated Short Acculturation Scale for Hispanics (SASH). …

Clustering Microbiome Data Using Mixtures Of Logistic Normal Multinomial Models, Yuan Fang, Sanjeena Subedi

Pharmacy Faculty Scholarship

Discrete data such as counts of microbiome taxa resulting from next-generation sequencing are routinely encountered in bioinformatics. Taxa count data in microbiome studies are typically high-dimensional, over-dispersed, and can only reveal relative abundance therefore being treated as compositional. Analyzing compositional data presents many challenges because they are restricted to a simplex. In a logistic normal multinomial model, the relative abundance is mapped from a simplex to a latent variable that exists on the real Euclidean space using the additive log-ratio transformation. While a logistic normal multinomial approach brings flexibility for modeling the data, it comes with a heavy computational cost …

Coronavirus Update 9-7-23, The Coronavirus Planning Team

University Briefings & Virtual Events

Many of you are already aware that a new strain has caused an uptick in COVID cases across the nation. In the interest of everyone’s health and safety, we want to remind you please not to go to class or work if you are feeling sick.

Large-Scale Functional Hyperconnectivity Patterns In Trauma-Related Dissociation: An Rs-Fmri Study Of Ptsd And Its Dissociative Subtype, Saurabh B. Shaw, Braeden A. Terpou, Maria Densmore, Jean Theberge, Pau Frewen, Margaret C. Mckinnon, Ruth A. Lanius

Department of Medicine Publications

The dissociative subtype of post-traumatic stress disorder (PTSD) is a distinct PTSD phenotype characterized by trauma-related dissociation, alongside unique patterns of functional connectivity. However, disparate findings across multiple scales of investigation have highlighted the need for a cohesive understanding of dissociative neurobiology. We took a step towards this goal by conducting one of the broadest region of interest (ROI)-to-ROI analyses performed on a PTSD population to date. In this retrospective study, we investigated resting-state functional MRI data collected from a total of 192 participants, 134 of whom were diagnosed with PTSD. Small functional connectivity differences (maximum effect size 0.27) were …

A Narrative Review Of The Many Psychiatric Manifestations Of Neurosyphilis: The Great Imitator, Baneet Kaur, Deepesh Khanna

HPD Articles

Neurosyphilis is an infection of the central nervous system caused by the spirochete, Treponema pallidum. New syphilis infections have been increasing around the world each year. This disease was much of a concern in the pre-penicillin era, where when left untreated many cases progressed to tertiary syphilis which can commonly manifest as neurosyphilis. Of particular interest, neurosyphilis has been linked to masquerading itself as various psychiatric conditions. This narrative review focuses on exploring psychiatric manifestations of neurosyphilis as well as the importance of screening in psychiatric settings and clinicians maintaining high clinical suspicion of the disease. A systematic search …

An Evolutionary Pathway For Coping With Emerging Infectious Disease, Scott Lyell Gardner, Daniel R. Brooks, Walter A. Boeger, Eric P. Hoberg

Zea E-Books Collection

Emerging infectious disease (EID) represents an existential threat to humanity. EIDs are increasing in frequency and impact because of climate change and other human activities. We are losing the battle against EIDs because of improper assessment of the risk of EID. This stems from adherence to a failed paradigm of pathogen-host associations that suggests EIDs ought to be both unpredictable and rare. That, in turn, leads to policies suggesting that crisis response is the best we can do. Real-time and phylogenetic assessments show EIDs to be neither rare nor unpredictable—this is the parasite paradox that shows the failures of the …

The Public Health Impact Of Paxlovid Covid-19 Treatment In The United States, Yuan Bai, Zhanwei Du, Lin Wang, Eric H. Y. Lau, Isaac Fung, Petter Holme, Ben Cowling, Alison Galvani, Robert Krug, Lauren Ancel Meyers

Biostatistics, Epidemiology & Environmental Health Sciences: Faculty Publications

The antiviral drug Paxlovid has been shown to rapidly reduce viral load. Coupled with vaccination, timely administration of safe and effective antivirals could provide a path towards managing COVID-19 without restrictive non-pharmaceutical measures. Here, we estimate the population-level impacts of expanding treatment with Paxlovid in the US using a multi-scale mathematical model of SARS-CoV-2 transmission that incorporates the within-host viral load dynamics of the Omicron variant. We find that, under a low transmission scenario (Re∼1.2) treating 20% of symptomatic cases would be life and cost saving, leading to an estimated 0.26 (95% CrI: 0.03, 0.59) million hospitalizations averted, 30.61 (95% …

Continuous Glucose Monitors To Reduce Ed Burden, Aneka Khilnani, Kevin Cho

URGENT Matters

No abstract provided.

Astrocytes In Stroke-Induced Neurodegeneration: A Timeline, Eileen Collyer, Elena Blanco-Suarez

Farber Institute for Neuroscience Faculty Papers

Stroke is a condition characterized by sudden deprivation of blood flow to a brain region and defined by different post-injury phases, which involve various molecular and cellular cascades. At an early stage during the acute phase, fast initial cell death occurs, followed by inflammation and scarring. This is followed by a sub-acute or recovery phase when endogenous plasticity mechanisms may promote spontaneous recovery, depending on various factors that are yet to be completely understood. At later time points, stroke leads to greater neurodegeneration compared to healthy controls in both clinical and preclinical studies, this is evident during the chronic phase …

A Rare Case Of Recurrent Parathyroid Adenomas After Initial Parathyroidectomy, Grant N. Schalet, Luke Vincent, Carl Eguez, Gerardo Diaz, Mark S. Shachner

HPD Articles

Hyperparathyroidism usually presents asymptomatically with elevated levels of calcium and parathyroid hormone; this biochemical imbalance establishes the diagnosis. In 80-85% of cases of primary hyperparathyroidism, singular parathyroid adenomas occur. In rare cases, this problem occurs due to multiple adenomas, multiglandular hyperplasia, or parathyroid carcinoma. Recurrent primary hyperparathyroidism (R-PHPT), as demonstrated in this case, is defined as hypercalcemia that arises after six months of normocalcemia following initial surgery for PHPT. The aim of this report is to describe the diagnosis and management of three parathyroid adenomas in a patient, two of which occurred after an initial partial parathyroidectomy.

Cocaine-Induced Four-Extremity Ischemia Caused By A Hypercoagulable State, Victoria Echevarria, Alexandra C. Echevarria, Damian Casadesus

HPD Articles

The use of cocaine is associated with serious complications including coronary vasospasm and myocardial, renal, intestinal, and neurological ischemia. Among these feared complications lies limb ischemia which is a rare potential side effect of chronic cocaine use. We present the case of a 50-year-old female with an extensive history of cocaine use who developed ischemia in all four limbs. Imaging studies revealed pulmonary emboli, multisystem thromboses, and microhemorrhages in the brain. Laboratory studies were significant for leukocytosis, thrombocytopenia, schistocytes on blood smear, and normal rheumatologic and hematologic studies. The patient was diagnosed with cocaine-induced thrombotic microangiopathy and she was treated …

Reducing Brain Kynurenic Acid Synthesis Precludes Kynurenine-Induced Sleep Disturbances, Katherine M. Rentschler, Snezana Milosavljevic, Annalisa M. Baratta, Courtney J. Wright, Maria V. Piroli, Zachary Tentor, Homayoun Valafar, Christian O'Reilly, Ana Pocivavsek

Publications

Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg−1; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF-04859989 (30 mg kg−1; s.c.); …

Braf V600e/Ras Mutations And Lynch Syndrome In Patients With Msi-H/Dmmr Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors, Raphael Colle, Sara Lonardi, Marine Cachanado, Michael J Overman, Elena Elez, Marwan Fakih, Francesca Corti, Priya Jayachandran, Magali Svrcek, Antoine Dardenne, Baptiste Cervantes, Alex Duval, Romain Cohen, Filippo Pietrantonio, Thierry André

Faculty, Staff and Student Publications

BACKGROUND: We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome (LS).

PATIENTS AND METHODS: Patients were defined as LS-linked if germline mutation was detected and as sporadic if loss of MLH1/PMS2 expression with BRAFV600E mutation and/or MLH1 promoter hypermethylation, or biallelic somatic MMR genes mutations were found. Progression-free survival (PFS) and overall survival (OS) were adjusted on prognostic modifiers selected on unadjusted analysis (P < .2) if limited number of events.

RESULTS: Of 466 included patients, 305 (65.4%) and 161 (34.5%) received, respectively, anti-PD1 alone and anti-PD1+anti-CTLA4 …

Nutrition-Related Experiences Of Women With Perinatal Depression During The Covid-19 Pandemic: A Qualitative Study, Dahlia Stott, Cynthia Klobodu, Lisa A. Chiarello, Bobbie Posmontier, Mona Egohail, Pamela A. Geller, June Andrews Horowitz, Brandy-Joe Milliron

College of Nursing Faculty Papers & Presentations

Women with perinatal depression are at a high risk for unhealthy dietary behaviors but whether the coronavirus disease 2019 (COVID-19) pandemic has exacerbated this risk is unknown. Here we report the findings of a qualitative study exploring the impact of the COVID-19 pandemic on nutrition-related experiences of women with perinatal depression. Using a qualitative descriptive approach, in-depth interviews were conducted with 18 women with a history of perinatal depression and 10 healthcare providers. A semistructured format elicited how food and nutrition-related behaviors of women with perinatal depression were affected by the COVID-19 pandemic. Thematic analysis identified 4 themes related to …

Paclitaxel With Or Without Cixutumumab As Second-Line Treatment Of Metastatic Esophageal Or Gastroesophageal Junction Cancer: A Randomized Phase Ii Ecog-Acrin Trial, Shannon Stockton, Paul Catalano, Steven J. Cohen, Barbara A, Burtness, Edith P. Mitchell, Efrat Dotan, Sam J. Lubner, Pankaj Kumar, Mary F. Mulcahy, George A. Fisher, Theodore L. Crandall, Al Benson

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers.

METHODS: The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated.

RESULTS: Median …

Evidence Of Neurovascular Water Exchange And Endothelial Vascular Dysfunction In Schizophrenia: An Exploratory Study, Eric L Goldwaser, Danny J J Wang, Bhim M Adhikari, Joshua Chiappelli, Xingfeng Shao, Jiaao Yu, Tong Lu, Shuo Chen, Wyatt Marshall, Alexa Yuen, Mark Kvarta, Yizhou Ma, Xiaoming Du, Si Gao, Osamah Saeedi, Heather Bruce, Patrick Donnelly, Hugh O'Neill, Alan R Shuldiner, Braxton D Mitchell, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

BACKGROUND AND HYPOTHESIS: Mounting evidence supports cerebrovascular contributions to schizophrenia spectrum disorder (SSD) but with unknown mechanisms. The blood-brain barrier (BBB) is at the nexus of neural-vascular exchanges, tasked with regulating cerebral homeostasis. BBB abnormalities in SSD, if any, are likely more subtle compared to typical neurological insults and imaging measures that assess large molecule BBB leakage in major neurological events may not be sensitive enough to directly examine BBB abnormalities in SSD.

STUDY DESIGN: We tested the hypothesis that neurovascular water exchange (Kw) measured by non-invasive diffusion-prepared arterial spin label MRI (n = 27 healthy controls [HC], n = …

Five-Year Follow-Up Of Keynote-087: Pembrolizumab Monotherapy For Relapsed/Refractory Classical Hodgkin Lymphoma, Philippe Armand, Pier Luigi Zinzani, Hun Ju Lee, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian Von Tresckow, Margaret A Shipp, Alex F Herrera, Jianxin Lin, Eunhee Kim, Samhita Chakraborty, Patricia Marinello, Craig H Moskowitz

Faculty, Staff and Student Publications

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received …

Prospective Assessment Of Inter-Rater Reliability Of A Neonatal Adverse Event Severity Scale., Thomas Salaets, Thierry Lacaze-Masmonteil, Isamu Hokuto, Cheri Gauldin, Amjad Taha, Anne Smits, Liesbeth Thewissen, Ilse Van Horebeek, Armuchou Shoraisham, Khorshid Mohammad, Manami Suzuki, Shiori Komachi, Kurt Michels, Mark A. Turner, Karel Allegaert, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: To ensure the quality of clinical trial safety data, universal data standards are required. In 2019 the International Neonatal Consortium (INC) published a neonatal adverse event severity scale (NAESS) to standardize the reporting of adverse event (AE) severity. In this study the reliability of AE severity grading with INC NAESS was prospectively assessed in a real-world setting. Methods: Severity of AEs was assessed by two independent observers at each of four centers across the world. In each center two series of 30 neonatal adverse events were assessed by both observers: in a first phase with a generic (Common Terminology …

Early Exposure To Added Sugars Via Infant Formula May Explain High Intakes Of Added Sugars During Complementary Feeding Beyond Maternal Modeling., Adrianne K. Griebel-Thompson, Tera L. Fazzino, Emily Cramer, Rocco A. Paluch, Katherine S. Morris, Kai Ling Kong

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Research has shown that early exposure to added sugars from table food is related to increased intake of added sugars in later childhood. The earliest window of exposure to added sugars may be in infancy via infant formula. However, beyond the well-established factors of maternal lifestyle and modeling, there is a lack of research examining how exposure to added sugars from infant formula influences infant/toddler added sugar intakes from table foods and sugar sweetened beverages (SSB).

OBJECTIVE: While accounting factors previously associated with infant/toddler added sugar intakes and maternal SSB consumption (proximal measure of maternal modeling), this study aims …

Seamless Phase Ii/Iii Design: A Useful Strategy To Reduce The Sample Size For Dose Optimization, Liyun Jiang, Ying Yuan

Faculty, Staff and Student Publications

Background: The traditional more-is-better dose selection paradigm, originally developed for cytotoxic chemotherapeutics, can be problematic when applied to the development of novel molecularly targeted agents. Recognizing this issue, the US Food and Drug Administration initiated Project Optimus to reform the dose optimization and selection paradigm in oncology drug development, emphasizing the need for greater attention to benefit-risk considerations.

Methods: We identify different types of phase II/III dose-optimization designs, classified according to trial objectives and endpoint types. Through computer simulations, we examine their operating characteristics and discuss the relevant statistical and design considerations for effective dose optimization.

Results: Phase II/III dose-optimization …

Atezolizumab For Advanced Alveolar Soft Part Sarcoma, Alice P Chen, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported.

METHODS: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action.

RESULTS: A total of 52 patients were evaluated. An objective response was observed in …

3d-Cultured Blastoids Model Human Embryogenesis From Pre-Implantation To Early Gastrulation Stages, Rowan M Karvas, Joseph E Zemke, Syed Shahzaib Ali, Eric Upton, Eshan Sane, Laura A Fischer, Chen Dong, Kyoung-Mi Park, Brian Chew, Brittany Meyer, Chao Zhou, Sabine Dietmann, Thorold W Theunissen, Et Al.

2020-Current year OA Pubs

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate the defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14. Extended blastoid culture results in the localized activation of primitive streak marker TBXT and the emergence of embryonic germ layers by day …

Heart Failure Burden In Oman As A Mid-East Exemplar Versus Global Perspectives: An Integrative Review, Maryam Alharrasi, Chandrani Isac, Joy Kabasindi Kamanyire

Journal of the Saudi Heart Association

Heart failure (HF), a clinical syndrome caused by a structural and functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and pulmonary congestion. This study intends to investigate the state of heart failure (HF) in Oman and assess it in comparison of global trends. Ten published literatures from the past 20 years were included after a thorough search of databases (Arab World Research Source, EBSCOhost, Medline, and Google Scholar). These studies were reviewed considering the global literature. We have observed an increase in HF cases especially in older adults, over the past two decades in Oman. Acute coronary syndrome …